TY - JOUR
T1 - The role of Notch signaling in diabetic endothelial progenitor cells dysfunction
AU - Sukmawati, Dewi
AU - Tanaka, Rica
AU - Ito-Hirano, Rie
AU - Fujimura, Satoshi
AU - Hayashi, Ayato
AU - Itoh, Seigo
AU - Mizuno, Hiroshi
AU - Daida, Hiroyuki
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Aims To investigate the role of Notch signaling pathway in vasculogenic dysfunction of diabetic EPCs (DM-EPCs). Methods The study was performed in mice and diabetes was induced with Streptozotocin. The functional consequences of Notch pathway modulation were studied by assessment of colony forming capacity (EPC colony forming assay), EPC differentiation capacity (% of definitive EPC-CFU (dEPC-CFU)), circulating EPCs (EPC culture assay) and migrated cells (migration assay); in the presence of Notch inhibitor (γ-secretase inhibitors (GSI)) compared to control. Notch pathway and VEGF involvement in DM- EPCs were assessed by gene expression (RT-qPCR). Results DM demonstrated to increase Notch pathway expression in bone marrow (BM) EPCs followed by lower EPC-CFU number, EPCs differentiation capacity, number of circulating EPCs, migrated cells and VEGF expression compared to control (p < 0.05). Inhibition of Notch pathway by GSI rescued vasculogenic dysfunction in DM-EPCs as represented by increase in EPC-CFU number, differentiation capacity and number of circulating EPCs (p < 0.05). Conclusion Our findings indicate the involvement of Notch pathway in mediating DM-EPCs dysfunction including less number of EPC-CFU, circulating EPCs and migrated cell number compared to control. Further in vitro inhibition of Notch pathway by GSI rescued DM-EPC dysfunction. Therefore targeting Notch pathway in DM may provide a target to restore DM-EPC dysfunction.
AB - Aims To investigate the role of Notch signaling pathway in vasculogenic dysfunction of diabetic EPCs (DM-EPCs). Methods The study was performed in mice and diabetes was induced with Streptozotocin. The functional consequences of Notch pathway modulation were studied by assessment of colony forming capacity (EPC colony forming assay), EPC differentiation capacity (% of definitive EPC-CFU (dEPC-CFU)), circulating EPCs (EPC culture assay) and migrated cells (migration assay); in the presence of Notch inhibitor (γ-secretase inhibitors (GSI)) compared to control. Notch pathway and VEGF involvement in DM- EPCs were assessed by gene expression (RT-qPCR). Results DM demonstrated to increase Notch pathway expression in bone marrow (BM) EPCs followed by lower EPC-CFU number, EPCs differentiation capacity, number of circulating EPCs, migrated cells and VEGF expression compared to control (p < 0.05). Inhibition of Notch pathway by GSI rescued vasculogenic dysfunction in DM-EPCs as represented by increase in EPC-CFU number, differentiation capacity and number of circulating EPCs (p < 0.05). Conclusion Our findings indicate the involvement of Notch pathway in mediating DM-EPCs dysfunction including less number of EPC-CFU, circulating EPCs and migrated cell number compared to control. Further in vitro inhibition of Notch pathway by GSI rescued DM-EPC dysfunction. Therefore targeting Notch pathway in DM may provide a target to restore DM-EPC dysfunction.
KW - Diabetes
KW - Endothelial progenitor cells
KW - Notch signaling pathway
KW - Vasculogenesis
KW - γ-Secretase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84951835580&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2015.09.015
DO - 10.1016/j.jdiacomp.2015.09.015
M3 - Article
C2 - 26598222
AN - SCOPUS:84951835580
SN - 1056-8727
VL - 30
SP - 12
EP - 20
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
IS - 1
ER -
